Our overall objectives remain to elucidate the mechanisms responsible for sudden cardiac death in patients with ischemic heart disease in terms of abnormalities in calcium fluxes across various cardiac membranes. Our goals for the current year have been to define further the mechanisms controlling calcium influx and efflux in sarcoplasmic reticulum vesicles isolated from both cardiac and skeletal muscle, and to identify the modes of action of fatty acids and their derivatives, which accumulate in and around the ischemic myocardium, on these calcium fluxes. The actions of antiarrhythmic drugs on these calcium fluxes is also under study. In addition, our group is studying the effects of ischemia on ion fluxes across the myocardial sarcolemma to define the mechanisms that alter these ionic currents in the ischemic heart.